Pentoxifylline is a drug shown in AIDS and cancer patients to reduce TNF in those patients with elevated levels. It reduces inflammation via several mechanisms and improves blood flow by decreasing viscosity. We have treated 24 patients with late radiation side effects. Most patients have symptoms in part due to combination therapy including surgery. At present, 20 patients have completed the initial protocol. Eighteen have improved. Some improvements have been dramatic. Improvements include active and passive range of motion, strength, alleviation of pain, and improved healing. Patients with late radiation effects were found to have elevated peripheral fibroblast growth factor (bFGF) and vasculoendothelial growth factor (VEGF) in approximately 80% of cases. Most patients with elevated FGF or VEGF had decreases in their blood cytokine level after treatment. We will continue to follow blood cytokine levels and in some patients measure skin blood flow and collagen type in affected tissues to establish the mechanism of the drugs effect. The results suggest that severe forms of late radiation effects are due in large part to chronically elevated cytokine levels. Further work is needed to determine whether anti-cytokine therapies will prevent these side effects and perhaps oncogenesis.